Techniques enabling the efficient transfer of a substance of interest from the external medium into cells, and particularly into cellular nuclei, are of considerable interest in the field of biotechnology. Such techniques may be useful for protein or peptide production, for regulation of gene expression, for analysis of intracellular signaling channels and for analysis of the effect of transporting a variety of different substances into a cell (or cell nucleus). Currently available techniques are often limited by the inability of a transfer vector to transfer biologically active substances into the cytoplasm (or nuclei) of cells in the host to be treated without affecting the host genome or altering the biological properties of the active substance.
Previously, transduction of large active substances into cells was limited by the size and biochemical properties of the substance being transported. However, recent progress in this field has been achieved with the use of transporter peptides or proteins. For example, Schwarze and colleagues described a 10-mer peptide derived from HIV, TAT48-57, which is capable of transporting conjugated peptides or proteins intracellularly into tissues and across the blood-brain barrier. Schwarze et al., Science 285:1573 (1999). These conjugated peptides or proteins are thought to be internalized by cells via a protein transduction process that does not involve endocytosis. This discovery opened a new methodology for biomedical research and for direct delivery of drugs into patients. However, one important limitation of this approach is the lack of cellular specificity for these types of transporters. Thus, adverse side effects from interaction with normal, non-target tissues limit the usefulness of many of these non-specific transporter peptides. Such a limitation is particularly problematic in the treatment of chronic diseases such as diabetes.
A need remains in the art for an efficient, safe compositions and methods for specifically targeting various cell types for the intracellular delivery of drugs and therapeutic agents via peptide transport.